phase (ph) ii bevacizumab + erlotinib for patients (pts) with recurrent malignant glioma (mg)

Conditions: Glioblastoma; Gliosarcoma

Summary: primary objective: to estimate 6-month progression free survival probability of pts w recurrent malignant gliomas treated w erlotinib + bevacizumab. secondary objectives: to evaluate safety \& tolerability of erlotinib + bevacizumab among pts w recurrent malignant gliomas to evaluate radiographic response of pts w recurrent malignant gliomas treated w erlotinib + bevacizumab to evaluate pharmacokinetics of erlotinib when administered to pts w recurrent malignant gliomas; \& to examine relationship of clinical response to epidermal growth factor (egfr) expression, amplification, \& v-iii mutation, phosphatase and tensin homolog (pten) expression, vascular endothelial growth factor (vegf) expression, vascular endothelial growth factor receptor 2 (vegfr-2) \& phosphorylated protein kinase b (pkb/akt) in archival tumor samples

exploratory, phase ii study designed to assess anti-tumor activity of combinatorial regimen consisting of erlotinib + bevacizumab among pts w recurrent malignant glioma. signal transduction inhibitors, such as erlotinib, as well as anti-angiogenic agents, such as bevacizumab, are expected to exert a cytostatic anti-tumor effect. primary endpoint of study is probability of progression-free survival at 6 months. an important secondary objective is to further assess the safety of erlotinib + bevacizumab for pts w rmg. pharmacokinetic studies included in protocol will evaluate impact of enzyme-inducing anti-epileptic drugs (eiaeds) on metabolism of erlotinib. if study demonstrates that combo regimen of erlotinib + bevacizumab is associated w encouraging anti-tumor activity among pts w recurrent malignant glioma (rmg), further assessment of regimen in additional ph ii \& possibly ph iii studies, will be considered.

Eligibility criteria:
inclusion criteria: * pts have histologically confirmed diagnosis of recurrent/progressive who gr iii \& iv mg \& meet following inclusion criteria: * age \>18 yrs * interval of \>4 wks since prior surgery * interval of \>4 wks since prior external beam radiation therapy (xrt) or chemo, unless there is unequivocal evidence of progressive disease \& pts have recovered from all anticipated toxicity of most recent therapy * karnofsky performance status score \>60 * hematocrit \> 29 percent, absolute neutrophil count (anc) \>1,500 cells/microliter, platelets \>100,000 cells/microliter * serum creatinine \<.5mg/dl, blood urea nitrogen (bun) \<25 mg/dl, serum glutamate oxaloacetate transaminase (sgot) \& bilirubin \<1.5 x upper limit of normal (uln) * for pts on corticosteroids, they have been on stable dose for 1 wk prior to entry * pts have had prior bevacizumab are eligible however interval of \>6 wks must have elapsed since their last dose * signed informed consent approved by institutional review board (irb) prior to patient entry; * if sexually active, pts must agree to take contraceptive measures for duration of treatments exclusion criteria: * prior therapy w either bevacizumab/egfr-directed agents * \>3 prior recurrences * pregnancy/breast feeding * co-medication w immuno-suppressive agents other than corticosteroids including but not limited to cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil * evidence of central nervous system (cns) hemorrhage on baseline mri on ct scan * pts who require therapeutic anti-coagulation * uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring iv antibiotics \& psychiatric illness/social situations that would limit compliance w study requirements, or disorders associated w significant immunocompromised state * pts w another primary malignancy that has required treatment within past year * pts w acute/chronic renal insufficiency/those w acute renal insufficiency of any severity due to hepato-renal syndrome/in peri-operative liver transplantation period

Keywords: glioblastoma gliosarcoma recurrent mg malignant glioma glioma glioblastoma multiforme (gbm) gbm brain tumor anaplastic astrocytoma anaplastic oligodendroglioma anaplastic oligoastrocytoma bevacizumab avastin erlotinib tarceva